Dual anti-angiogenesis agents bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer: results of a phase II study
Mené en Australie sur 45 patients atteints d'un cancer colorectal de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de contrôle de la maladie à 6 mois, et la toxicité d'un traitement de première ligne combinant bévacizumab et trébananib
Purpose:To assess the efficacy and safety of dual anti-angiogenesis agents, bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer (mCRC). Experimental Design:Open label Phase II study enrolled patients with unresectable mCRC with no prior systemic treatment. All patients received bevacizumab 7.5mg/kg 3-weekly and trebananib 15 mg/kg weekly. The primary endpoint was disease control (stable disease, partial (PR) or complete responses (CR)) at 6 months (DC6m). Secondary endpoints included toxicity, response rate (ORR), progression-free survival (PFS) and overall survival (OS). Exploratory biomarkers in plasma angiogenesis-related proteins, tumour gene expression and plasma antibodies to tumour antigens were examined. Results:45 patients were enrolled from four Australian sites. DC6m was 63% (95% CI: 47-77). ORR was 17% (95% CI: 7-32), comprising 7 PRs. Median duration of response was 20 months (range 10-48 months). Median PFS was 8.4 months and median OS 31.4 months. G1-2 peripheral oedema and joint-related symptoms were common. Overall incidence of G3-4 adverse events (AEs) of any type was 33% (n=15). Expected AEs of bevacizumab treatment did not appear to be increased by the addition of trebananib. Conclusions:In a first-line mCRC population, the dual anti-angiogenic combination, bevacizumab plus trebananib, was efficacious with durable responses. The toxicity profile of the combination was manageable and did not exceed that expected with bevacizumab +/-chemotherapy. Exploratory biomarker results suggest that in addition to its anti-angiogenic activity, this combination may provide clinical benefit by enabling anti-tumour immunomodulatory effects, supporting ongoing trials of anti-angiogenic therapy combined with cancer immunotherapy.